1. Field of the Invention
This invention relates to a novel macromolecular mitomycin C derivative having low toxicity and excelling in the antitumor activity, and methods for the production of the derivative and the salt.
2. Prior Art Statement
In recent years, numerous known antibiotics have been demonstrated as possessing an outstanding antitumor activity. Among the antitumor antibiotics introduced to the art, mitomycin C is a representative antitumor agent produced in Japan. It produces an outstanding curative effect on sarcoma, leukemia, deciduocellular sarcoma, epithelioma, and cancer of the bladder and has been finding extensive utility in clinical applications.
While the mitomycin C possesses a remarkable antitumor effect, however, it exhibits strong toxicity to normal cells and induces discernible side effects such as decreases in leukocytes and thrombocytes, accelerated hemorrhage, and hepatic disorders. In the administration of mitomycin C, these side effects should be carefully considered so as not to induce them.
When the antitumor active substance of such a low molecular compound as mitomycin C is conjugated to a macromolecular compound, this antitumor active substance is gradually released from the macromolecular compound in the patient's body, retains its concentration in the blood, is allowed to vary the body distribution and, therefore, is expected to inhibit the side effects and increase the antitumor activity.
As respects the mitomycin C, the combination thereof with dextran, a plasma extender, has been known as what will answer the expectation just mentioned (Japanese Patent Public Disclosure SHO 54(1979)-97691. Since dextran, a natural produce, is difficult of chemical modification, the ratio of fixed mitomycin C in the conjugate is only about 10% at most.
In the circumstances, there has existed an earnest desire for a macromolecular compound capable of combining mitomycin C therewith in a high ratio.